Porphobilinogen (PBG) tetramerizes enzymatically to produce uroporphyrinogen III, the precursor of heme, cytochromes and chlorophyll. In order to determine the mechanism of this reaction, we intend to synthesize a C14-labelled dimer of PBG (DPM-III). DPM-III-C14 and unlabelled PBG will be incubated with the avian erythrocyte system which synthesizes heme. Heme will be isolated as hemin, converted to protoporphyrin IX and the latter degraded to hematinic acid (HA) and methylethylmaleimide (MEM). A mechanism involving a single initial rearrangement of PBG and subsequent head-to-tail condensations would yield labeled MEM and unlabeled HA. An insertion mechanism would yield labeled HA and unlabeled MEM.